3D printed tablets containing oxaliplatin loaded alginate nanoparticles for colon cancer targeted delivery. An in vitro/in vivo study.

This study aimed to develop a colon-targeted tablet of oxaliplatin (OP) using the combination of nanotechnology and fused deposition modeling (FDM) 3D printing to improve its antitumor activity, tumor targetability, and safety profile. Eudragit L100-55 filament containing OP loaded alginate nanoparticles (OP-NPs) were fabricated using hot-melt extrusion method and printed by an FDM printer to 3D printed tablets with good uniformity in the drug content and selective release of OP in the colonic environment. The antitumor effect of 3D printed tablets containing OP-NPs in CT-26 tumor-bearing mice was evaluated compared to intravenous and oral administration of OP solution, and compressed tablets containing OP-NPs, which were prepared by direct compression method with the same formulation. The antitumor effect of 3D printed tablets containing OP-NPs was remarkable and comparable with intravenous OP solution (p Ëƒ 0.05) with a better safety profile, whereas compressed tablets did not show any significant antitumor effect, probably in terms of non-selective drug release in stomach and upper intestine environments. This study highlights the potential of the combination of nanotechnology and 3D printing in the preparation of colon-specific drug delivery systems of chemotherapeutic drugs with good antitumor activity, tumor targetability, and safety profile for colorectal cancer treatment.

Preparation and characterization of 3D printed PLA microneedle arrays for prolonged transdermal drug delivery of estradiol valerate.

Biodegradable polymeric microneedle arrays (BPMNAs) could be explored as potential devices for transdermal drug delivery, which can provide a painless and safe drug delivery method. BPMNAs could also provide high drug-loading capacity and prolonged drug delivery once integrated with a drug reservoir. However, the fabrication of MNAs with a drug reservoir is expensive and requires complicated procedures. The present study was conducted to describe the preparation of a reservoir-based BPMNA containing estradiol valerate using polylactic acid (PLA) with the combination of FDM 3D printing and injection volume filling techniques. The tip size of the 3D printed needles decreased to 173 µm utilizing a chemical etching process. The content of estradiol valerate loaded in the 3D printed PLA MNAs was 29.79 ± 0.03 mg, and the release was in a prolonged manner for up to 7 days. The results of mechanical tests revealed that the force needed for the 3D printed PLA MNAs fracture (900 N) was significantly higher than that needed for their skin penetration (4 N). The successful penetration of 3D printed PLA MNAs through the stratum corneum was confirmed via penetration test, methylene blue staining, and histological examination. The results showed that 3D printed PLA MNAs can penetrate into the skin without reaching to the dermal nerves and puncture of blood vessels. In conclusion, in the current study, we explored the practicability of the preparation of drug loaded reservoir-based BPMNAs using the combination of FDM 3D printing and injection volume filling techniques for painless and prolonged transdermal drug delivery.

Preparation and characterization of polypills containing aspirin and simvastatin using 3D printing technology for the prevention of cardiovascular diseases.

Three-dimensional (3D) printing has become a promising manufacturing technique for pharmaceutical products. Fused deposition modeling (FDM) is the most affordable printing technology. But this technique has two major drawbacks: limited drug-loading capacity and the stability of thermolabile drugs. So, other techniques such as melt casting could be associated with FDM to overcome these limitations. In the melt casting method, the drug is mixed with a molten polymer and is poured in the mold and allowed to solidify. The present study for the first time describes the preparation of a multi-compartment polypill permits the physical separation of incompatible drugs by combination of FDM and melt casting techniques. A two-compartment polypill was made using FDM by Eudragit® L100-55 and simultaneously its compartments were filled by aspirin and simvastatin containing molten PEG 6000. Simultaneous usage of FDM and melt casting techniques could increase the drug-loading capacity of 3D-printed polypills. The low temperatures used in melt casting and the absence of solvent in this method would warrant the integrity of polypills, the complete separation of incompatible drugs, and their stability. The prepared polypills showed good uniformity in drug content which confirms the precision of FDM and melt casting techniques. Drug interaction was investigated before and after the accelerated stability test using DSC, which showed that 3D-printed polypills successfully preserved drugs from the interaction. For the first time, this study demonstrates the feasibility of the combination of FDM and melt casting techniques as an innovative platform for CVD polypills production.